The research will develop model structural systems to study the molecular details of polypeptide chain elongation during protein synthesis. The three-dimensional structure of the E. coli elongation factor Tu will be determined to high resolution (2.5A) by X-ray crystallographic techniques. Using difference Fourier methods, the refined structure will be used as the basic model to study the atomic details of the conformational changes that occur in Tu as the protein interacts with allosteric effectors and other macromolecules to accomplish its function and with antibiotics to inhibit its function during protein synthesis. The structure-function relationships in Tu will be compared to those of other allosteric enzymes, if known, to determine if similar or new correlations between structure and function can be made. Biochemical and crystallization studies will be conducted to develop the complexes, Tu-Ts and Tu-GTP-aminoacyl-tRNA, as well as the E. coli elongation factor G, into viable projects for three-dimension X-ray diffraction analyses. The structural studies of the Tu complexes will provide a direct visualization of protein-protein and protein-nucleic acid interactions in three dimensions. In addition, the structure of a Tu-GTP-aminoacyl-tRNA complex may answer numerous questions about one aspect of editing mechanisms in protein synthesis, that of Tu's ability to bind only to non-initiator, aminoacyl-tRNAs. Structure-function studies of the G factor will provide a model for the protein which may suggest mechanisms for translocation of the peptidyl-tRNA on the ribosome during protein synthesis.